tbuckley/cabot-search huggingface dataset:
A Primer on Systematic Review and Meta-analysis in Diabetes Research
Authors: Deirdre K. Tobias, Stefania Papatheodorou, Jennifer M. Yamamoto, Frank B. Hu
Journal: Diabetes Care (2023)

A systematic review is a rigorous process that involves identifying, selecting, and synthesizing available evidence pertaining to an a priori–defined research question. The resulting evidence base may be summarized qualitatively or through a quantitative analytic approach known as meta-analysis. Systematic review and meta-analysis (SRMAs) have risen in popularity across the scientific realm including diabetes research. Although well-conducted SRMAs are an indispensable tool in informing evidence-based medicine, the proliferation of SRMAs has led to many reviews of questionable quality and misleading conclusions. The objective of this article is to provide up-to-date knowledge and a comprehensive understanding of strengths and limitations of SRMAs. We first provide an overview of the SRMA process and offer ways to identify common pitfalls at key steps. We then describe best practices as well as evolving approaches to mitigate biases, improve transparency, and enhance rigor. We discuss several recent developments in SRMAs including individual-level meta-analyses, network meta-analyses, umbrella reviews, and prospective meta-analyses. Additionally, we outline several strategies that can be used to enhance quality of SRMAs and present key questions that authors, editors, and readers should consider in preparing or critically reviewing SRMAs.
The Relationship Between Alcohol Consumption, BMI, and Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis
Authors: Laura Llamosas-Falcón, Jürgen Rehm, Sophie Bright, Charlotte Buckley, Tessa Carr, Carolin Kilian, Aurélie M. Lasserre, Julia M. Lemp, Yachen Zhu, Charlotte Probst
Journal: Diabetes Care (2023)

Background Moderate alcohol use may be associated with lower risk of type 2 diabetes mellitus (T2DM). Previous reviews have reached mixed conclusions. Purpose To quantify the dose-response relationship between alcohol consumption and T2DM, accounting for differential effects by sex and BMI. Data Sources Medline, Embase, Web of Science, and one secondary data source. Study Selection Cohort studies on the relationship between alcohol use and T2DM. Data Extraction Fifty-five studies, and one secondary data source, were included with a combined sample size of 1,363,355 men and 1,290,628 women, with 89,983 and 57,974 individuals, respectively, diagnosed with T2DM. Data Synthesis Multivariate dose-response meta-analytic random-effect models were used. For women, a J-shaped relationship was found with a maximum risk reduction of 31% (relative risk [RR] 0.69, 95% CI 0.64–0.74) at an intake of 16 g of pure alcohol per day compared with lifetime abstainers. The protective association ceased above 49 g per day (RR 0.82, 95% CI 0.68–0.99). For men, no statistically significant relationship was identified. When results were stratified by BMI, the protective association was only found in overweight and obese women. Limitations Our analysis relied on aggregate data. We included some articles that determined exposure and cases via self-report, and the studies did not account for temporal variations in alcohol use. Conclusions The observed reduced risk seems to be specific to women in general and women with a BMI ≥25 kg/m2. Our findings allow for a more precise prediction of the sex-specific relationship between T2DM and alcohol use, as our results differ from those of previous studies.
Administering [177Lu]Lu-PSMA-617 Prior to Radical Prostatectomy in Men with High-risk Localised Prostate Cancer (LuTectomy): A Single-centre, Single-arm, Phase 1/2 Study
Authors: Renu S. Eapen, James P. Buteau, Price Jackson, Catherine Mitchell, Sheng F. Oon, Omar Alghazo, Lachlan McIntosh, Nattakorn Dhiantravan, Mark J. Scalzo, Jonathan O'Brien, Shahneen Sandhu, Arun A. Azad, Scott G. Williams, Gaurav Sharma, Mohammad B. Haskali, Mathias Bressel, Kenneth Chen, Pocharapong Jenjitranant, Aoife McVey, Daniel Moon, Nathan Lawrentschuk, Paul J. Neeson, Declan G. Murphy, Michael S. Hofman
Journal: European Urology (2023)
Prior antibiotic administration disrupts anti-PD-1 responses in advanced gastric cancer by altering the gut microbiome and systemic immune response
Authors: Chang Gon Kim, June-Young Koh, Su-Jin Shin, Ji-Hee Shin, Moonki Hong, Hyun Cheol Chung, Sun Young Rha, Hyo Song Kim, Choong-Kun Lee, Ji Hyun Lee, Yejeong Han, Hyoyong Kim, Xiumei Che, Un-Jung Yun, Hyunki Kim, Jee Hung Kim, Seo Young Lee, Su Kyoung Park, Sejung Park, Hyunwook Kim, Jin Young Ahn, Hei-Cheul Jeung, Jeong Seok Lee, Young-Do Nam, Minkyu Jung
Journal: Cell Reports Medicine (2023)

Evidence on whether prior antibiotic (pATB) administration modulates outcomes of programmed cell death protein-1 (PD-1) inhibitors in advanced gastric cancer (AGC) is scarce. In this study, we find that pATB administration is consistently associated with poor progression-free survival (PFS) and overall survival (OS) in multiple cohorts consisting of patients with AGC treated with PD-1 inhibitors. In contrast, pATB does not affect outcomes among patients treated with irinotecan. Multivariable analysis of the overall patients treated with PD-1 inhibitors confirms that pATB administration independently predicts worse PFS and OS. Administration of pATBs is associated with diminished gut microbiome diversity, reduced abundance of Lactobacillus gasseri, and disproportional enrichment of circulating exhaustive CD8+ T cells, all of which are associated with worse outcomes. Considering the inferior treatment response and poor survival outcomes by pATB administration followed by PD-1 blockade, ATBs should be prescribed with caution in patients with AGC who are planning to receive PD-1 inhibitors.
International patterns and trends in the incidence of melanoma and cutaneous squamous cell carcinoma, 1989–2020
Authors: Catherine M Olsen, Nirmala Pandeya, Bruna S Ragaini, Rachel E Neale, David C Whiteman
Journal: British Journal of Dermatology (2023)

Abstract Background Cutaneous squamous cell carcinoma (cSCC) and melanoma have different associations with sun exposure. Objectives To compare trends in the incidence rates of cSCC and melanoma, to provide insight into changing patterns of exposure to ultraviolet radiation (UVR). Methods We compared trends in the incidence of cSCC and melanoma in seven susceptible populations residing at mid-to-high latitudes: Finland, Norway, Sweden, Denmark, Scotland, the Netherlands and Tasmania (Australia). We fitted Joinpoint models to describe trends in age-standardized incidence rates for melanoma and cSCC and calculated the average annual percentage rate of change for the period 1989–2020 (1989–2018 for Tasmania). We calculated the incident rate ratio (IRR) as the ratio of the age-standardized rates (European Standard Population) for cSCC to melanoma and conducted age–period–cohort modelling to compare age, period and cohort effects. Results The ratio of cSCC-to-melanoma incidence increased with proximity to the equator and over time. In the most recent time period, the incidence of cSCC was higher than the incidence of melanoma for men and women in all seven populations. While the ratio of cSCC-to-melanoma incidence was higher for men vs. women, in most countries the cSCC-to-melanoma IRR increased over time to a greater extent in women than in men. Melanoma incidence was higher among younger people and cSCC incidence was higher among older people; the age at which the incidence of cSCC overtook the incidence of melanoma was progressively younger with proximity to the equator. Conclusions Despite concerted international efforts to preserve the ozone layer over the past four decades resulting in significant reductions in surface ultraviolet B at mid-latitudes, the incidence of skin cancer, particularly cSCC, continues to rise in those regions. Our findings are consistent with a stronger association with age-associated cumulative sun exposure for cSCC vs. melanoma and suggest that women are currently receiving greater UV radiation exposure than in the past.
Sequential multi-omics analysis identifies clinical phenotypes and predictive biomarkers for long COVID
Authors: Kaiming Wang, Mobin Khoramjoo, Karthik Srinivasan, Paul M.K. Gordon, Rupasri Mandal, Dana Jackson, Wendy Sligl, Maria B. Grant, Josef M. Penninger, Christoph H. Borchers, David S. Wishart, Vinay Prasad, Gavin Y. Oudit
Journal: Cell Reports Medicine (2023)

The post-acute sequelae of COVID-19 (PASC), also known as long COVID, is often associated with debilitating symptoms and adverse multisystem consequences. We obtain plasma samples from 117 individuals during and 6 months following their acute phase of infection to comprehensively profile and assess changes in cytokines, proteome, and metabolome. Network analysis reveals sustained inflammatory response, platelet degranulation, and cellular activation during convalescence accompanied by dysregulation in arginine biosynthesis, methionine metabolism, taurine metabolism, and tricarboxylic acid (TCA) cycle processes. Furthermore, we develop a prognostic model composed of 20 molecules involved in regulating T cell exhaustion and energy metabolism that can reliably predict adverse clinical outcomes following discharge from acute infection with 83% accuracy and an area under the curve (AUC) of 0.96. Our study reveals pertinent biological processes during convalescence that differ from acute infection, and it supports the development of specific therapies and biomarkers for patients suffering from long COVID.
Selective control of transposable element expression during T cell exhaustion and anti–PD-1 treatment
Authors: Pierre-Emmanuel Bonté, Christina Metoikidou, Sandrine Heurtebise-Chretien, Yago A. Arribas, Aurélien Sutra Del Galy, Mengliang Ye, Leticia Laura Niborski, Elina Zueva, Eliane Piaggio, Agathe Seguin-Givelet, Nicolas Girard, Cécile Alanio, Marianne Burbage, Christel Goudot, Sebastian Amigorena
Journal: Science Immunology (2023)

In chronic infections and cancer, T cells are exposed to prolonged antigen stimulation, resulting in loss of function (or exhaustion) and impairment of effective immunological protection. Exhausted T cells are heterogeneous and include early progenitors (Tpex) and terminally exhausted cells (Tex). Here, we used bulk and single-cell transcriptomics to analyze expression of transposable elements (TEs) in subpopulations of mouse and human CD8+ tumor-infiltrating T lymphocytes (TILs). We show that in mice, members of the virus-like murine VL30 TE family (mostly intact, evolutionary young ERV1s) are strongly repressed in terminally exhausted CD8+ T cells in both tumor and viral models of exhaustion. Tpex expression of these VL30s, which are mainly intergenic and transcribed independently of their closest gene neighbors, was driven by Fli1, a transcription factor involved in progression from Tpex to Tex. Immune checkpoint blockade (ICB) in both mice and patients with cancer increased TE expression (including VL30 in mice), demonstrating that TEs may be applicable as ICB response biomarkers. We conclude that expression of TEs is tightly regulated in TILs during establishment of exhaustion and reprogramming by ICB. Analyses of TE expression on single cells and bulk populations open opportunities for understanding immune cell identity and heterogeneity, as well as for defining cellular gene expression signatures and disease biomarkers.
Quality of End-of-Life Care Among Adolescents and Young Adults With Cancer
Authors: Jennifer W. Mack, Colin Cernik, Hajime Uno, Cecile A. Laurent, Lauren Fisher, Lanfang Xu, Julie Munneke, Nancy Cannizzaro, Mallory Casperson, Corey M. Schwartz, Joshua R. Lakin, Robert M. Cooper, Andrea Altschuler, Lori Wiener, Chun R. Chao, Lawrence Kushi
Journal: Journal of Clinical Oncology (2023)

Adolescents, young adults with cancer receive limited psychosocial and spiritual support near death.
Role of the NLRP1 inflammasome in skin cancer and inflammatory skin diseases
Authors: Laura Calabrese, Zeno Fiocco, Mark Mellett, Rui Aoki, Pietro Rubegni, Lars E French, Takashi K Satoh
Journal: British Journal of Dermatology (2023)

Inflammasomes are cytoplasmic protein complexes that play a crucial role in protecting the host against pathogenic and sterile stressors by initiating inflammation. Upon activation, these complexes directly regulate the proteolytic processing and activation of proinflammatory cytokines interleukin (IL)-1β and IL-18 to induce a potent inflammatory response, and induce a programmed form of cell death called pyroptosis to expose intracellular pathogens to the surveillance of the immune system, thus perpetuating inflammation. There are various types of inflammasome complexes, with the NLRP1 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-1) inflammasome being the first one identified and currently recognized as the predominant inflammasome sensor protein in human keratinocytes. Human NLRP1 exhibits a unique domain structure, containing both an N-terminal pyrin (PYD) domain and an effector C-terminal caspase recruitment domain (CARD). It can be activated by diverse stimuli, such as viruses, ultraviolet B radiation and ribotoxic stress responses. Specific mutations in NLRP1 or related genes have been associated with rare monogenic skin disorders, such as multiple self-healing palmoplantar carcinoma; familial keratosis lichenoides chronica; autoinflammation with arthritis and dyskeratosis; and dipeptidyl peptidase 9 deficiency. Recent research breakthroughs have also highlighted the involvement of dysfunctions in the NLRP1 pathway in a handful of seemingly unrelated dermatological conditions. These range from monogenic autoinflammatory diseases to polygenic autoimmune diseases such as vitiligo, psoriasis, atopic dermatitis and skin cancer, including squamous cell carcinoma, melanoma and Kaposi sarcoma. Additionally, emerging evidence implicates NLRP1 in systemic lupus erythematosus, pemphigus vulgaris, Addison disease, Papillon-Lefèvre syndrome and leprosy. The aim of this review is to shed light on the implications of pathological dysregulation of the NLRP1 inflammasome in skin diseases and investigate the potential rationale for targeting this pathway as a future therapeutic approach.
RBPMS regulates cardiomyocyte contraction and cardiac function through RNA alternative splicing
Authors: Peiheng Gan, Zhaoning Wang, Svetlana Bezprozvannaya, John R McAnally, Wei Tan, Hui Li, Rhonda Bassel-Duby, Ning Liu, Eric N Olson
Journal: Cardiovascular Research (2023)

Abstract Aims RNA binding proteins play essential roles in mediating RNA splicing and are key post-transcriptional regulators in the heart. Our recent study demonstrated that RBPMS (RNA binding protein with multiple splicing) is crucial for cardiac development through modulating mRNA splicing, but little is known about its functions in the adult heart. In this study, we aim to characterize the post-natal cardiac function of Rbpms and its mechanism of action. Methods and results We generated a cardiac-specific knockout mouse line and found that cardiac-specific loss of Rbpms caused severe cardiomyocyte contractile defects, leading to dilated cardiomyopathy and early lethality in adult mice. We showed by proximity-dependent biotin identification assay and mass spectrometry that RBPMS associates with spliceosome factors and other RNA binding proteins, such as RBM20, that are important in cardiac function. We performed paired-end RNA sequencing and RT–PCR and found that RBPMS regulates mRNA alternative splicing of genes associated with sarcomere structure and function, such as Ttn, Pdlim5, and Nexn, generating new protein isoforms. Using a minigene splicing reporter assay, we determined that RBPMS regulates target gene splicing through recognizing tandem intronic CAC motifs. We also showed that RBPMS knockdown in human induced pluripotent stem cell-derived cardiomyocytes impaired cardiomyocyte contraction. Conclusion This study identifies RBPMS as an important regulator of cardiomyocyte contraction and cardiac function by modulating sarcomeric gene alternative splicing.
SMPDL3A is a cGAMP-degrading enzyme induced by LXR-mediated lipid metabolism to restrict cGAS-STING DNA sensing
Authors: Yanfei Hou, Zhimeng Wang, Peiyuan Liu, Xubiao Wei, Zhengyin Zhang, Shilong Fan, Lulu Zhang, Fangping Han, Yikang Song, Ling Chu, Conggang Zhang
Journal: Immunity (2023)
Mapping of neuronal and glial primary cilia contactome and connectome in the human cerebral cortex
Authors: Jun Yao Wu, Su-Ji Cho, Katherine Descant, Peter H. Li, Alexander Shapson-Coe, Michal Januszewski, Daniel R. Berger, Cailyn Meyer, Cristine Casingal, Ariba Huda, Jiaqi Liu, Tina Ghashghaei, Mikayla Brenman, Michelle Jiang, Joseph Scarborough, Art Pope, Viren Jain, Jason L. Stein, Jiami Guo, Ryohei Yasuda, Jeff W. Lichtman, E.S. Anton
Journal: Neuron (2023)
pH-Responsive NIR-II phototheranostic agents for in situ tumor vascular monitoring and combined anti-vascular/photothermal therapy
Authors: Shuaishuai Bian, Xiuli Zheng, Weimin Liu, Zekun Gao, Yingpeng Wan, Jihao Li, Haohui Ren, Wenjun Zhang, Chun-Sing Lee, Pengfei Wang
Journal: Biomaterials (2023)
Reducing scope 3 carbon emissions in gastrointestinal endoscopy: results of the prospective study of the ‘Green Endoscopy Project Würzburg’
Authors: Dorothea Henniger, Thomas Lux, Max Windsheimer, Markus Brand, Alexander Weich, Theodor Kudlich, Katrin Schöttker, Alexander Hann, Alexander Meining
Journal: Gut (2023)

Objective Carbon emissions generated by gastrointestinal endoscopy have been recognised as a critical issue. Scope 3 emissions are mainly caused by the manufacturing, packaging and transportation of purchased goods. However, to our knowledge, there are no prospective data on the efficacy of measurements aimed to reduce scope 3 emissions. Design The study was performed in a medium-sized academic endoscopy unit. Manufacturers of endoscopic consumables were requested to answer a questionnaire on fabrication, origin, packaging and transport. Based on these data, alternative products were purchased whenever possible. In addition, staff was instructed on how to avoid waste. Thereafter, the carbon footprint of each item purchased was calculated from February to May 2023 (intervention period), and scope 3 emissions were compared with the same period of the previous year (control period). Results 26 of 40 companies answered the questionnaire. 229 of 322 products were classified as unfavourable. A switch to alternative items was possible for 47/229 items (20.5%). 1666 endoscopies were performed during the intervention period compared with 1751 examinations during the control period (−4.1%). The number of instruments used decreased by 10.0% (3111 vs 3457). Using fewer and alternative products resulted in 11.5% less carbon emissions (7.09 vs 8.01 tons of carbon equivalent=tCO2 e). Separation of waste led to a reduction of 20.1% (26.55 vs 33.24 tCO2e). In total, carbon emissions could be reduced by 18.4%. Conclusion Use of fewer instruments per procedure, recycling packaging material and switching to alternative products can reduce carbon emissions without impairing the endoscopic workflow.
Navigating the ‘new normal’: what guidelines exist for postpartum return to physical activity and sport? A scoping review
Authors: Jenna M Schulz, Hana Marmura, Chloe M Hewitt, Laura J Parkinson, Jane S Thornton
Journal: British Journal of Sports Medicine (2023)

Objective Women are often advised to return to activity (RTA) as early as 6 weeks postpartum, despite undergoing significant physical, physiological and psychological changes. Our objective was to examine existing evidence and clinical practice guidelines to navigate a safe and successful RTA or return to sport (RTS) postpartum. Methods We searched CINAHL, Embase, Medline, PsycINFO and SPORTDiscus and included any secondary studies with recommendations or guidelines for RTA or RTS postpartum. Grey literature and primary sources were excluded. Four reviewers independently screened titles and abstracts, followed by full-text review for eligibility, with conflicts resolved by a third-party reviewer. One reviewer extracted data, which was cross-referenced by another reviewer. Results 5851 studies were screened, and 33 were included in this scoping review. Most studies stated that RTS postpartum can begin once ‘medically safe’, around 6 weeks postpartum, but this term was generally left undefined. In addition, most studies recommended engaging in 150 min of moderate-vigorous physical activity per week after 6 weeks postpartum, but the type of exercise recommended was often non-specific. Conclusion A lack of consistent, evidence-based guidelines exist for RTA or RTS postpartum. Multiple evidence gaps require additional research to inform patient and activity specific guidelines for a safe and successful RTA or RTS postpartum.
<i>In utero</i> or early-in-life exposure to antibiotics and the risk of childhood atopic dermatitis, a population-based cohort study
Authors: Zelma Chiesa Fuxench, Nandita Mitra, Domenica Del Pozo, Ole Hoffstad, Daniel B Shin, Sinéad M Langan, Irene Petersen, Ketaki Bhate, David J Margolis
Journal: British Journal of Dermatology (2023)

Abstract Background Atopic dermatitis (AD) is a common inflammatory disease of the skin that begins early in life and can be lifelong. The purpose of our study was to evaluate whether fetal exposure and/or early-life exposure of a child to antibiotics increases the risk of early-onset AD. Objectives We hypothesize that antibiotic exposure in utero or early in life (e.g. first 90 days) increases the likelihood that children develop AD. Methods Utilizing a large, prospectively collected electronic medical records database, we studied the association of antibiotic exposure received in utero or very early in life and the relative risk of onset of AD in a population-based cohort study. Associations were estimated using proportional hazards models as hazard ratios (HRs) with 95% confidence intervals (CIs). Results The risk of AD in childhood was increased after in utero or early-life antibiotic exposure. For any in utero antibiotic exposure the HR (CI) was 1.38 (1.36–1.39). However, penicillin demonstrated the strongest association with AD for both in utero exposure [1.43 (1.41–1.44)] and for childhood exposure [1.81 (1.79–1.82)]. HRs were higher in children born to mothers without AD than in those with AD pointing to effect modification by maternal AD status. Conclusions Children born to mothers exposed to antibiotics while in utero had, depending on the mother’s history of AD, approximately a 20–40% increased risk of developing AD. Depending on the antibiotic, children who received antibiotics early in life had a 40–80% increased risk of developing AD. Our study supports and refines the association between incident AD and antibiotic administration. It also adds population-based support to therapeutic attempts to treat AD by modifying the skin microbiome.